Tag Archives: Alzheimer’s

New Hope To Fight Alzheimer’s

It is known that the onset of Alzheimer’s disease (AD) is associated with the accumulation of Amyloid beta () peptides in small molecular clusters known as oligomers. These trigger the formation of so-called ‘neurofibrillary tangles’ within neurons hamper their workings, ultimately causing cell death and so significant cognitive decline. Very large Aβ oligomers which form plaques outside neurons, alongside neuroinflammation have also been found to play a key part in the progression of the disease.


The EU-funded iRhom2 in AD project took as its starting point the protein iRhom2, which has been identified as a genetic risk factor for AD due to its pro-inflammatory properties. The team were able to explore further the influence of iRhom2 on neuroinflammation in mice. iRhom2 recently emerged as a protein of note in AD as it aids the maturation of an enzyme called TACE (tumor necrosis factor-α converting enzyme) guiding it towards a cell’s plasma membrane where the enzyme releases a cell-signalling cytokine (TNFα), implicated in the regulation of inflammatory processes. While mice studies have shown that TNFα-dependent inflammation can lead to sepsis and rheumatoid arthritis, it is also thought that the process contributes to neuroinflammatory signalling events, which can cause harm in the brain.

The EU-funded iRhom2 in AD project worked with mice that are prone to develop the hallmarks of AD, amyloid plaques and memory deficits. The team genetically altered iRhom2 in the mice then analysed the progression of the pathology using an array of biochemical and histological methods, together with a number of behavioural tests to assess cognitive decline. The results were somewhat surprising.

We initially hypothesised that iRhom2 would affect one specific aspect of neuroinflammation in AD. What we discovered was even more exciting as it actually affects several different aspects of neuroinflammation simultaneously. So modulating iRhom2 appears particularly well suited to interfere with AD,” explains project coordinator Prof. Dr. Stefan Lichtenthaler.

Source: https://cordis.europa.eu/

Brain Metals Drive Alzheimer’s Progression

Alzheimer’s disease could be better treated, thanks to a breakthrough discovery of the properties of the metals in the brain involved in the progression of the neurodegenerative condition, by an international research collaboration including the University of Warwick.

Iron is an essential element in the brain, so it is critical to understand how its management is affected in Alzheimer’s disease. The advanced X-ray techniques that we used in this study have delivered a step-change in the level of information that we can obtain about iron chemistry in the amyloid plaques. We are excited to have these new insights into how amyloid plaque formation influences iron chemistry in the human brain, as our findings coincide with efforts by others to treat Alzheimer’s disease with iron-modifying drugs,” commented Dr Joanna Collingwood, from Warwick’s School of Engineering, who was part of a research team which characterised iron species associated with the formation of amyloid protein plaques in the human brainabnormal clusters of proteins in the brain. The formation of these plaques is associated with toxicity which causes cell and tissue death, leading to mental deterioration in Alzheimer’s patients.

They found that in brains affected by Alzheimer’s, several chemically-reduced iron species including a proliferation of a magnetic iron oxide called magnetite – which is not commonly found in the human brainoccur in the amyloid protein plaques. The team had previously shown that these minerals can form when iron and the amyloid protein interact with each other. Thanks to advanced measurement capabilities at synchrotron X-ray facilities in the UK and USA, including the Diamond Light Source I08 beamline in Oxfordshire, the team has now shown detailed evidence that these processes took place in the brains of individuals who had Alzheimer’s disease. They also made unique observations about the forms of calcium minerals present in the amyloid plaques.

The team, led by an EPSRC-funded collaboration between University of Warwick and Keele University – and which includes researchers from University of Florida and The University of Texas at San Antonio – made their discovery by extracting amyloid plaque cores from two deceased patients who had a formal diagnosis of Alzheimer’s. The researchers scanned the plaque cores using state-of-the-art X-ray microscopy at the Advanced Light Source in Berkeley, USA and at beamline I08 at the Diamond Light Source synchrotron in Oxfordshire, to determine the chemical properties of the minerals within them.

Source: https://warwick.ac.uk/

Compound to treat Alzheimer’s shows promise in mice

Researchers at The Rockefeller University in New York have made a component, RU-505, which can be used to slow the progression of Alzheimer’s disease in mice.

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The investigations build on Alzheimer’s studies conducted in Rockefeller University labs, particularly research focused on how the cells of the brain process the amyloid precursor protein (APP). Faulty regulation of APP processing — in which APP is chopped into smaller pieces during normal brain cell metabolism — is believed to contribute to the development of Alzheimer’s. Scientists in the Fisher Center work on understanding why APP can sometimes produce protein fragments that are safely secreted from the cell and at other times produce a protein called amyloid-ß, a major component of the brain plaques that are a hallmark of Alzheimer’s disease.

Source: https://www.rockefeller.edu/

Learning How To Create And Keep Memories

Drug manufacturers are looking at ways to alleviate memory loss, one of the most distressing symptoms of diseases such as Alzheimer’s. Professor George Kemenes from the Sussex University (UK) intends to show how such drugs could work.


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The goal is to identify brain molecules that are crucial for the building up and maintenance of long-term memory,’ he says. ‘We aim to find ways to manipulate these molecules to enable us to control functions and improve the speed at which animals learn, or help them remember for longer periods of time. This would then link into drug development for humans.’

Pond snails are ideal for this kind of study because they share important characteristics with humans. These include the basic molecular mechanisms that control long-term memory and learning. These mechanisms involve the activation or suppression of a protein, CREB, which is key to the formation of long-term memory. CREB is present in species ranging from molluscs and flies to rats and humans.

Memory responses can be tested with classic Pavlovian experiments. Snails exposed to the smell of pear drops followed by food still respond weeks later to the smell by moving their mouth parts in anticipation of food. This ‘flashbulbmemory is created by just one exposure to the two stimuli. The snails have a memory associating the smell of pear drops with the arrival of food – a learned and remembered response.

In a similar test, a snail is exposed to a mildly unpleasant stimulus by touching its head with a paintbrush (snails don’t like being tickled) before food is introduced. It takes much longer for the snail to associate an unpleasant stimulus with the arrival of food. Recently, George has succeeded in inhibiting the quickly learned memory and improving the weaker, more slowly-acquired memory at molecular level.

Working in collaboration with colleagues at the University, key findings include the discovery that amyloid peptides, substances that are thought to underlie Alzheimer’s disease in humans, also cause memory loss in snails. Another finding is that age-related memory loss in snails can be prevented by treatment with a small peptide known as PACAP.

Source: http://www.sussex.ac.uk/